Luteinizing hormone-releasing hormone targeted poly(methyl vinyl ether maleic acid) nanoparticles for doxorubicin delivery to MCF-7 breast cancer cells

Abstract

The purpose of this study was to design a targeted anti-cancer drug delivery system for breast cancer. Therefore, doxorubicin (DOX) loaded poly(methyl vinyl ether maleic acid) nanoparticles (NPs) were prepared by ionic cross-linking method using Zn(2+) ions. To optimise the effect of DOX/polymer ratio, Zn/polymer ratio, and stirrer rate a full factorial design was used and their effects on particle size, zeta potential, loading efficiency (LE, %), and release efficiency in 72 h (RE72, %) were studied. Targeted NPs were prepared by chemical coating of tiptorelin/polyallylamin conjugate on the surface of NPs by using 1-ethyl-3-(3-dimethylaminopropyl) carboiimid HCl as cross-linking agent. Conjugation efficiency was measured by Bradford assay. Conjugated triptorelin and targeted NPs were studied by Fourier-transform infrared spectroscopy (FTIR). The cytotoxicity of DOX loaded in targeted NPs and non-targeted ones were studied on MCF-7 cells which overexpress luteinizing hormone-releasing hormone (LHRH) receptors and SKOV3 cells as negative LHRH receptors using Thiazolyl blue tetrazolium bromide assay. The best results obtained from NPs prepared by DOX/polymer ratio of 5%, Zn/polymer ratio of 50%, and stirrer rate of 960 rpm. FTIR spectrum confirmed successful conjugation of triptorelin to NPs. The conjugation efficiency was about 70%. The targeted NPs showed significantly less IC50 for MCF-7 cells compared to free DOX and non-targeted NPs.

Fig. 1

Contribution of different effective factors on the particle size, zeta potential, drug loading efficiency (LE %), drug release after 72 h (RE₇₂ %)

Fig. 2

Effect of different levels of studied parameters on the particle size, zeta potential, loading efficiency and drug release efficiency of DOX loaded PMVEMA NPs

Fig. 3

DOX release profile from different studied PMVEMA NPs

Fig. 4

FTIR spectrum of a Triptorelin b Polyallylamine c Conjugated triptorelin/polyallylamine

Fig. 5

FTIR spectrum of a Non‐targeted b Targeted NPs

Fig. 6

TEM micrographs of optimized formulation of doxorubicin loaded NPs

Fig. 7

Viability of a MCF‐7 b SKOV3 cells after treatment with different concentrations of targeted and non‐targeted NPs with or without DOX compared to free DOX by MTT assay